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Atg9 resides on a unique population of small vesicles in presynaptic nerve terminals

ABSTRACT: In neurons, autophagosomes are mainly initiated in distal axons, followed by maturation during retrograde transport. Autophagosomal growth depends on the supply of membrane lipids which requires small vesicles containing Atg9, a lipid scramblase essential for autophagocytosis. Here, we show that Atg9 vesicles are enriched in synapses and resemble synaptic vesicles in size and density. The proteome of Atg9 vesicles immunoisolated from nerve terminals showed conspicuously low levels of trafficking proteins except of the AP2-complex and some enzymes involved in endosomal phosphatidylinositol metabolism. Super resolution microscopy of nerve terminals and isolated vesicles revealed that Atg9-vesicles represent a distinct vesicle population with limited overlap not only with synaptic vesicles but also other membranes of the secretory pathway, uncovering a surprising heterogeneity in their membrane composition. Our results are compatible with the view that Atg9-vesicles function as lipid shuttles that scavenge membrane lipids from various intracellular membranes to support autophagosome biogenesis.

INSTRUMENT(S): Q Exactive HF-X, Q Exactive HF

ORGANISM(S): Rattus Norvegicus (rat)

TISSUE(S): Brain

SUBMITTER: Aleksandar Chernev

LAB HEAD: Henning Urlaub

PROVIDER: PXD041702 | Pride | 2024-01-17

REPOSITORIES: Pride

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2022-12-24 | PXD037490 | Pride

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2016-11-02 | GSE89407 | GEO

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Impaired presynaptic proteostasis in the initial stages of amyloid beta proteotoxicity

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